We sought to improve the efficacy of LAK + IL-2 therapy by administering it intraperitoneally to patients with cancer limited to this anatomic space. Patients underwent priming with interleukin-2 and harvesting of LAK precursor cells as is done on the systemic LAK and IL-2 trials. The cells were administered intraperitoneally daily for five days along with interleukin-2 at a dose of 25,000 units per kilograms every eight hours. Of ten evaluable colon carcinoma patients, five had partial responses, and of nine patients with ovarian carcinoma, two had partial responses. All responses were judged either by peritoneoscopy or by laparotomy and tended to be of short duration (four months). Toxic effects of this therapy were similar to those observed in patients receiving LAK and IL-2 therapy systemically with the exception that our patients routinely developed diffuse abdominal swelling and rebound abdominal tenderness. LAK activity was not maintained in the peritoneal cavity unless interleukin-2 was administered concurrently. LAK activity was observed in the peritoneal cavity for a minimum of five consecutive days while IL-2 was being administered. Activity fell back to baseline approximately 48 hours after discontinuation of intraperitoneal infusions of IL-2. Gamma interferon levels rose appreciably in the peritoneal fluid and there was evidence from monocyte activation in vivo. Intraperitoneal fibrosis limited the delivery of therapy beyond approximately three cycles. We conclude that this therapy is effective in bringing about tumor responses and is reasonably well tolerated. However, fibrosis in the peritoneal cavity will ultimately prevent the effective delivery of this therapy.